Interest is growing rapidly in the field of oncology in the anti-obesity drug target that has recently been investigated in large retrospective studies and preclinical models
Glucagon like peptide-1 (GLP-1) is an endocrine hormone produced in the intestine, pancreas and brain that plays a key role in the regulation of blood glucose, lipid metabolism and appetite (Endocr Rev. 2021;42:101–132). Initially approved for the treatment of type 2 diabetes, GLP-1 receptor agonists (GLP-1 RAs) have now emerged as novel blockbuster anti-obesity drugs that effectively enhance satiety and lead to reduced calorie intake (Am J Med. 2025;138:934–940).
It is becoming increasingly apparent that GLP-1 RAs may have an expanding role beyond the treatment of obesity and type 2 diabetes. Clinical benefits have been documented in a range of other disorders, including cardiovascular disease, non-alcoholic fatty liver disease, sleep apnoea, rheumatoid arthritis and neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases (Signal Transduct Target Ther. 2024;9:234; eClinicalMedicine. 2025;86:103363). Recently, a link has also been suggested between GLP-1 RA use and reduced cancer risk among obesity-related cancers. Large retrospective analyses based on US electronic health records have reported a reduced risk of 10 obesity-related cancers over a 15-year follow-up period in patients with type 2 diabetes prescribed GLP-1 RAs compared with those taking insulin (JAMA Netw Open. 2024;7:e2421305), and in adults with obesity treated with GLP-1 RAs versus non-users (JAMA Oncol. 2025;e252681). In the latter analysis, a significantly lower overall risk of cancer was reported in those taking versus not taking GLP-1 RAs over a 10-year period (13.6 per 1,000 person-years [PY] versus 16.4 per 1,000 PY; hazard ratio [HR] 0.83; 95% confidence interval [CI] 0.76–0.91; p=0.002). The largest reductions in risk were seen for endometrial (HR 0.75; p=0.05) and ovarian (HR 0.53; p=0.04) cancer and meningioma (HR 0.69; p=0.05). A possible increased risk of thyroid cancer related to GLP-1 RA use has been reported in epidemiological analyses (Cancer. 2024;17:78), but not in a large observational study (Thyroid. 2025;35:69–78), although follow-up was relatively short.
Potential links between GLP-1 RA-induced weight loss and a positive effect on cancer have been explored in preclinical models of a number of obesity-related tumours, including endometrial (Gynecol Oncol. 2024;191:116–123) and pancreatic (NPJ Metab Health Dis. 2025;3:10). The animal models show consistent and encouraging data in that rodents, like humans, experience significant weight loss and improvements in biomarkers of metabolic health in response to GLP-1RA treatment. This is an important finding because substantial weight loss is believed to be required to influence the mechanisms relating to major changes in hormone levels, inflammation and immune response driving obesity-related cancer (J Acad Nutr Diet. 2018;118:652–667). Marked intentional weight loss appears to be associated with metabolic and immune reprogramming, resulting in a switch from an obese, immunosuppressed, inflamed and metabolically impaired environment to a healthy immune environment characterised by increased cancer-killing T-cells and reduced inflammation (Biomark Res. 2025;13:50, Cancer Metastasis Rev. 2022;41:607–625). Interestingly, our unpublished data suggest similar effects on systemic hormones, immune cells and tumour growth are observed when food intake is matched in GLP-1 RA-treated and non-treated animals, suggesting that GLP-1 RAs are exerting their effects indirectly as a result of the positive immune and metabolic changes that occur with significant weight loss.
Currently it is unknown whether all cancers will be equally responsive to weight-loss therapy, but epidemiological preclinical data suggest there will be differences; for example, hormone receptor-positive breast cancers appear to be less responsive than other obesity-related cancers, such as endometrial cancer, to GLP-1 RA-induced weight loss, possibly due to an interaction between different metabolic pathways (JAMA Netw Open. 2024;7:e2421305).
The molecular mechanisms underlying the effects of GLP-1 RAs on tumour development and progression are incompletely understood, and many questions remain unanswered regarding their clinical use as trials are yet to be conducted to specifically evaluate the effect of GLP-1 RAs on cancer patient outcomes. However, it is likely that GLP-1 RAs will play an important role in the management of at least some of the key obesity-related malignancies in the near future (Cancer Drug Resist. 2024;7:49; J Natl Cancer Inst 2025. doi: 10.1093/jnci/djaf163). A recently published UK modelling simulation of 22 cancers, in fact, has predicted that a reduction of almost 21,500 cancer cases could be achieved over 10 years if 50% of patients with obesity lowered their body mass index by 1 category with GLP-1 RA treatment (Cancer Epidemiol. 2025;97:102837).
Programme details
Opportunities for targeting glucagon like peptide-1 (GLP-1) in cancer prevention and treatment. ESMO Congress 2025 - Special Symposium
